title: Oligosaccharide conjugates of Bordetella pertussis and bronchiseptica induce bactericidal antibodies, an addition to pertussis vaccine.
abstract: Pertussis is a highly contagious respiratory disease that is especially dangerous for infants and children. Despite mass vaccination, reported pertussis cases have increased in the United States and other parts of the world, probably because of increased awareness, improved diagnostic means, and waning vaccine-induced immunity among adolescents and adults. Licensed vaccines do not kill the organism directly; the addition of a component inducing bactericidal antibodies would improve vaccine efficacy. We investigated Bordetella pertussis and Bordetella bronchiseptica LPS-derived core oligosaccharide (OS) protein conjugates for their immunogenicity in mice. B. pertussis and B. bronchiseptica core OS were bound to aminooxylated BSA via their terminal Kdo residues. The two conjugates induced similar anti-B. pertussis LPS IgG levels in mice. B. bronchiseptica was investigated because it is easier to grow than B. pertussis. Using B. bronchiseptica genetically modified strains deficient in the O-specific polysaccharide, we isolated fractions of core OS with one to five repeats of the terminal trisaccharide, having at the nonreducing end a GlcNAc or GalNAc, and bound them to BSA at different densities. The highest antibody levels in mice were elicited by conjugates containing an average of 8-17 OS chains per protein and with one repeat of the terminal trisaccharide. Conjugate-induced antisera were bactericidal against B. pertussis, and the titers correlated with ELISA-measured antibody levels (r = 0.74). Such conjugates are easy to prepare and standardize; added to a recombinant pertussis toxoid, they may induce antibacterial and antitoxin immunity.
authors.affiliation: Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, MD 20892, USA. kielbj@mail.nih.gov
authors.forename: Joanna
authors.initials: J
authors.lastname: Kubler-Kielb
authors.forename: Evgeny
authors.initials: E
authors.lastname: Vinogradov
authors.forename: Teresa
authors.initials: T
authors.lastname: Lagergård
authors.forename: Ariel
authors.initials: A
authors.lastname: Ginzberg
authors.forename: Jerry D
authors.initials: JD
authors.lastname: King
authors.forename: Andrew
authors.initials: A
authors.lastname: Preston
authors.forename: Duncan J
authors.initials: DJ
authors.lastname: Maskell
authors.forename: Vince
authors.initials: V
authors.lastname: Pozsgay
authors.forename: Jerry M
authors.initials: JM
authors.lastname: Keith
authors.forename: John B
authors.initials: JB
authors.lastname: Robbins
authors.forename: Rachel
authors.initials: R
authors.lastname: Schneerson
mesh_terms: D000818:Animals; D000907:Antibodies, Bacterial / Q000096:biosynthesis*; D016950:Bordetella bronchiseptica / Q000276:immunology / Q000378:metabolism*; D001886:Bordetella pertussis / Q000276:immunology / Q000378:metabolism*; D002240:Carbohydrate Sequence; D004591:Electrophoresis, Polyacrylamide Gel; D005260:Female; D051379:Mice; D008969:Molecular Sequence Data; D009844:Oligosaccharides / Q000737:chemistry / Q000378:metabolism*; D010567:Pertussis Vaccine / Q000008:administration & dosage* / Q000276:immunology; D019032:Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization
chemical_list: D000907:Antibodies, Bacterial; D009844:Oligosaccharides; D010567:Pertussis Vaccine